Vaccination is the best known and most successful application of immunological principles to human health. To be introduced and approved, a vaccine must be effective and the efficacy of all vaccines is reviewed from time to time. An effective vaccine must: induce the desired immune response; be stable on storage; and have sufficient immunogenicity. With non-living vaccines, in particular it is often necessary to control the release of the antigen following administration.
The binding of an antigen to a suspended amino acid has been shown to result in the slow release of the antigen following administration, thereby increasing safety whilst optimising efficacy by prolonging exposure. However, the manufacture of formulations comprising such antigens is problematic since the adsorption of the antigen to the amino acid results in undesired chemical by products that need to be removed. Furthermore, the process must be performed under sterile conditions. As the final product is a suspension it cannot be sterilised by filtration and as the active component is biological it cannot be heat sterilised. Accordingly, sterile suspensions are often manufactured by centrifugation within an aseptic suite.
U.S. Pat. No. 4,070,455 describes finely divided micro-particles of tyrosine having a glutaraldehyde treated allergen dispersed therein. The micro-particles are prepared by mixing a solution of tyrosine in a strong aqueous acid with a solution of glutaraldehyde treated ragweed pollen and then neutralising the resultant solution. The micro-fine particles of tyrosine containing the modified allergen are removed by centrifugation.
EP 0988862 describes the formulation of an antigen, a TH-1 inducing adjuvant and a sparingly water soluble amino acid for use in immunisation. The formulation is prepared by mixing a solution of an antigen and the TH1-inducing adjuvant with a solution of the sparingly soluble amino acid or derivative in a strong aqueous acid whilst neutralising the mixture of solutions, thereby co-precipitating the sparingly soluble amino acid and antigen. The resulting precipitate is removed from the solution by centrifugation, reconstituted with fresh buffer and the adjuvant added.
The use of centrifugation to remove the amino acid/antigen precipitate requires a substantial degree of aseptic exposure and a high dependency on operator interaction. The present invention addresses this problem.